Risk of Venous Thrombotic Events (VTE) in Patients with Myelodysplastic Syndromes with 5q Deletion during Lenalidomide Therapy: Single Institution Experience

Introduction: Lenalidomide (LEN) has been known to increase the risk of venous thromboembolism (VTE) in patients treated for multiple myeloma, non-Hodgkin lymphomas and myelodysplastic syndrome (MDS) with and without 5q deletion. The current recommendations are to place patients on anticoagulation. We hereby describe the frequency of VTE in patients with MDS with 5q Syndrome treated with single agent LEN off protocol in a single institution.

Methods: We performed data extraction from Mayo clinic records (October 1993 to March 2016) for patients with confirmed 5q Syndrome (5q + one abnormality except -7/7qdel and bone marrow blast <5%), after obtaining appropriate IRB approval. All cases were confirmed by our institution hematopathological review. Response was assessed by the International Working Group criteria for MDS (Cheson et al, Blood 2006). Prognostic factors were analyzed by univariate and multivariate analysis. Survival estimates were calculated using Kaplan-Meier curves and univariate and multivariate analysis was based on log-rank testing using JMP software version 10.

Results: Out of 1222 patients with MDS, 39 patients (3%) were identified with confirmed diagnosis of 5q Syndrome; 19 (2%) of which were treated with LEN. Median age was 69 years (56-87), with 58% being males. Median hemoglobin was 10.4 gm/dL (7.7-11.7), white blood cell count (WBC) 4.7 x10⁹/L (1.1-8.7), platelets of 153 x10⁹/L (63-805), and median bone marrow blasts 1%(0-7). Risk stratification per IPSS-R was either very low or low risk in 38% and 62%, respectively. Median erythropoietin level prior to LEN start was 90 (21-1937). Transformation into acute myeloid leukemia was found in 16% of the cases, with a median overall survival of 52 months.

Hematological improvement (HI) was achieved in 58% of the patients. In 11 cases repeat bone marrow biopsies and cytogenetic reassessment was done, 4 (40%) patients achieved complete cytogenetic remission. Median response duration was 25.9 months. Thirteen (68%) of the 19 patients were taking anticoagulation (3 warfarin, 1 rivaroxaban) or antiplatelet therapy (9 aspirin) while 6 patients did not take any anticoagulation during LEN therapy. VTE was found in 2 (11%) patients both of which were on anticoagulation (1 on aspirin, and one on warfarin). None of the 6 patients who were not taking anticoagulation therapy developed VTE.

Conclusion: MDS 5q Syndrome subgroup is a small cohort of patients representing 3% of all MDS patients. Anticoagulation was done in majority of patients with 5q Syndrome when treated with LEN. VTE was found to be an infrequent complication (11%) in patients treated with LEN and happened despite being on prophylactic anticoagulation. Larger size cohorts are needed to study this correlation further.